The Journal of Heart and Lung Transplantation Volume 23, Number 2S
non-rejectors. Eight developed graft coronary artery disease (CAD). All had at least 2 determinations for postTx alloantibodies. Overall 229 samples were analyzed. Results: Twenty-two of 45 had pre- and/or postTx antiHLA-ab: 77% in A (17/22) and only 22% in B (5/23), p ⫽ 0.0002. PreTx HLA-ab were present in 12 cases (27%): 8 class I⫹II and 4 class I. Presensitization was more frequent in A (11/ 22 ⫽ 50%) than in B (1/ 23 ⫽ 4%, p ⫽ 0.0005). Thirteen cases retained (8 cases) or developed (5 cases) antiHLA-ab during the 1st year postTx: 10 in A (50%) and 3 in B (13%), p ⫽ 0.0008. Late after Tx (⬎1year), antiHLA-ab were present in 8/18 (44%) in A and 3/22 (13.6%) in B (p ⫽ 0.03). Eleven exhibited de novo antibodies at any time postTx (6 class I⫹II, 4 class I and 1 class II): 7/22 in A (32%) and 4/23 in B (17%, p ⫽ 0.0004). Four of 8 cases with CAD (50%) had preformed antiHLA-ab (3 retained postTx) compared to 8 of 37 without CAD (25.6%), small sample size for statistical analysis (p ⫽ 0.09); none of CAD cases exhibited de novo antibodies. Conclusion: Preformed, persistent and de novo ELISA-detected antiHLA-ab were correlated with first-year acute rejection profile; further investigations with larger number of patients are needed to determine correlation with graft coronary disease. 103 BASILIXIMAB IN PEDIATRIC HEART TRANSPLANTATION INITIAL EXPERIENCE K.M. Ward,1 S.E. Crawford,2 S.G. Pophal,1 S.R. Rodgers,1 C.L. Backer,3 C. Mavroudis,3 E. Pahl,1 1Pediatric Cardiology, Northwestern Feinberg School of Medicine, Chicago, IL; 2 Pathology, Northwestern Feinberg School of Medicine, Chicago, IL; 3Cardiovascular and Thoracic Surgery, Northwestern Feinberg School of Medicine, Chicago, IL Background: Basiliximab (Bas), a chimeric monoclonal antibody against the CD25 chain of IL-2, has not been reported in pediatric heart transplant (Htx) recipients for rejection prophylaxis. We evaluated the safety and short-term efficacy of Bas in pediatric Htx recipients. Methods: A retrospective chart review included patients who received Bas on days 0 and 4 post Htx and a historical control group with no induction prophylaxis. Both groups received a calcineurin inhibitor, mycophenolate and steroids. Sensitized patients (PRA ⬎ 10%) were excluded. Evidence of hypersensitivity to Bas in the first week and incidence of rejection, infection and early PTLD were noted for the first year post Htx. Rejection was defined as an endomyocardial biopsy grade ⱖ 1B (n ⫽ 40) if treated or a clinical episode that was treated (n ⫽ 7). Infection was defined as that requiring IV antibiotics and/or hospitalization. Comparisons were made using Chi-square and t-tests. Results: 24 subjects were included in the review (14 Bas, 10 controls). The initial diagnosis was congenital heart disease for 4 patients in each group, the others had cardiomyopathy. All subjects are currently alive 5–52 months post Htx. There were no hypersensitivity reactions or PTLD in either group.
Age at Htx # Infections/pt # Cath w/bx/pt # rejections/pt Total # bx ⬎/⫽ 3A Time to 1st ⫹ bx in mo.
Basiliximab, n ⴝ 14, mean (SD) [range]
Control, n ⴝ 10 mean (SD) [range]
9.4 (7.5) [0.5–22] 1.0 (1.4) [0–4] 8.0 (4.2) [0–13] 1.4 (1.5) [0–4] 2 2.4 (2.2) [0.2–7.1]
7.7 (8.7) [0.3–25] 1.7 (1.8) [0–5] 6.8 (6.7) [0–16] 2.5 (3.7) [0–12] 3 0.3 (0.2) [0.2–0.9]
n/s n/s n/s p ⫽ 0.03 n/s p ⫽ 0.03
Conclusions: Basiliximab appears safe and was well tolerated in pediatric Htx recipients. Treated patients had less rejection and delayed time to first rejection. A larger prospective study is needed to confirm efficacy in reducing rejection and assess risk of infection or PTLD.
104 EXPERIENCE WITH SIROLIMUS IN PEDIATRIC CARDIAC TRANSPLANT RECIPIENTS T.M. Shankel,#1 D.C. Cutler,#1 J.K. Johnston,#1 J.A. Fitts,#1 R.E. Chinnock,#1 1Pediatric Heart Transplant Program, Loma Linda University Children’s Hospital, Loma Linda, CA Sirolimus is a relatively new immunosuppressive agent which works synergistically with calcineurin inhibitors. Reported benefits of sirolimus include antiproliferative properties and decreased nephrotoxicity. Little experience with the use of sirolimus in pediatric cardiac transplant patients has been reported. Purpose: We report our experience with the use of sirolimus in a group of pediatric cardiac transplant recipients. Methods/Results: Of 398 pediatric cardiac transplant recipients 46 were placed on sirolimus from October 2000 through July 2003. Indications for the use of sirolimus included decreased renal function (25), chronic rejection (14), post transplant lymphoproliferative disorder (10) and re-transplantation (6). Two patients had sirolimus discontinued due to side effects; one at 15 days post sirolimus due to tremors, and one at 6 months post sirolimus due to periorbital and hand edema. Of the 44 patients remaining on sirolimus, side effects were few and included transient neutropenia in 6 patients and stomatitis in 2 pts. Of 22 pts with total cholesterols available after beginning sirolimus, 9 (40%) had cholesterols greater than 200. Patients were less likely to have elevated cholesterol if they were on pravastatin prior to beginning sirolimus (p ⬍ 0.05) For patients switched due to renal insufficiency, 2 year actuarial freedom from rejection was 88% prior and 72% after sirolimus (p ⫽ 0.2). There was no difference in sirolimus levels between those who did and those who did not reject. Six patients were diagnosed with hypertension while on sirolimus, four of these patients had pre-existing renal insufficiency. Transient diarrhea occured in 3 patients, at intervals ranging from 10 days to 7 months post sirolimus. Conclusion: Sirolimus is well tolerated in the pediatric cardiac transplant population. Actuarial freedom from rejection in those patients placed on sirolimus due to renal insufficiency did not significantly change. Hypercholesteremia was a common side effect and may be preventable with administration of pravastatin.
105 NON-ADHERENCE TO THERAPY IS A COMMON CAUSE OF DEATH IN ADOLESCENCE FOLLOWING HEART OR LUNG TRANSPLANTATION T. Lunnon-Wood,1 P. Aurora,1 P. Whitmore,1 M.J. Fenton,1 R. Radley-Smith,1 M. Elliott,1 1Department of Cardiothoracic Transplant, Great Ormond Street Hospital for Children, London, London, United Kingdom Aims To determine the prevalence of non-adherence to medication as a cause of post-transplant death in children and to determine risk factors for death caused by non-adherence. Methods Children who died following heart(H), heart-lung(HL) and bilateral lung(BL) transplants at our centre between April 1988 and April 2003 were classified according to whether non-adherence to therapy was a major cause of death (Gp A); non-adherence to therapy was a contributing factor to death (Gp B); non-adherence was not a factor (Gp C). Poor adherence to therapy prior to transplant was identified by objective criteria. Subject age at transplant (AAT); age at death (AAD); gender; transplant type; and pre-transplant diagnosis were also investigated as potential risk factors. Analysis was by ANOVA and Tukeys HSD or Chi2 as appropriate. Risk factors were